Patients with diabetes mellitus may have exacerbated, protracted or non-resolving endodontic periapical lesions. Furthermore, current endodontic therapy for these and other patients focuses on eliminating the etiology, without enhancement of host regenerative mechanisms or suppression of host mediating factors. This research project seeks to determine the effects of diabetes mellitus on the development and progression of periapical lesions in the non-obese diabetic (NOD/LtJ) mouse model. This important preliminary work will act as a basis for planning clinical studies to investigate the pathophysiology of periapical lesions in diabetic patients and those with other systemic abnormalities that may affect healing of periapical lesions following endodontic treatment. Preliminary studies have shown that periapical lesions develop in normal mice and mice with the severe combined immune deficiency (scid) after exposing the pulp to the oral environment for 1-4 weeks. The bond-resorptive cytokines IL-1alpha and TNF-alpha were evident in periapical lesions of both strains, despite the absence of T- and B-cells in the scid mice. It is hypothesized that lesion progression occurred in these animals due to non-MNC II-mediated activation of macrophages as well as other non-specific immune reactions. Periapical lesions will be induced by exposing mandibular first molars in two groups of forth female mice: NOD/LtJ; and normal inbred BABL/cJ as controls. A control of the microbiological status of the exposed pulps will be attempted by initially testing the feasibility of sealing known anaerobes in the exposure cavities and recovering them after the test periods. The lesions will develop for 0, 2, 4, 8 and 12 weeks (each with n=8 animals, 16 teeth) after exposure. After euthanasia, the mandibular jaw blocks will be recovered, and processed for histologic, histomorphometric and immunohistochemical examination. This examination will include lesion size, inflammatory cell counts, and bone resorptive cytokine content.